A Study of Distal Jejunal-release Dextrose in Obese Participants

Phase 2Active Not RecruitingNCT05385978

Aphaia Pharma US LLC150 enrolled

Overview

The primary purpose of the study is to evaluate the efficacy and safety of APHD-012 (distal jejunal-release dextrose \[Aphaia technology, AT\]) in obese participants.

This is a randomized, double-blind, placebo-controlled, parallel-group, phase II proof-of-concept study to be conducted in 150 adult obese male and female participants who are 18 to 70 years of age with or without one or more endocrine and/or metabolic conditions. The study aims to evaluate the efficacy and safety of distal jejunal-release dextrose (Aphaia technology, AT) in obese participants. Participants will be randomly assigned to receive either APHD-012 (distal jejunal-release dextrose or APH-012P (a matching placebo). There will be two cohorts in the study. Participants from Cohort 1 will receive study medication once daily for 12 months (360 days), and participants from Cohort 2 will receive study medication once daily for 6 months (180 days). Overall, 150 participants will be enrolled in the study: * Cohort 1 (60 participants) - 6-month treatment period + 6-month maintenance treatment period * Cohort 2 (90 participants) - 6-month treatment period

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

150

Conditions

Obese

Interventions

APHD-012DRUG

Distal jejunal-release dextrose beads (Aphaia technology, AT)

APHD-012PDRUG

Distal jejunal-release placebo beads

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Body mass index 30.0-39.9 kg/m\^2 and/or waist circumference: men \>102 cm, women \>88 cm * Stable body weight: gain or loss in body weight ≤5 kg over last 3 months * Obese participants with or without one or more of the following conditions: 1. NAFLD - simple steatosis based on a FibroScan CAP™ test result at screening (CAP Score ≥238 decibel-milliwatts (dB/m) (Steatosis Grades 1-3) with no or mild fibrosis (F0-F1 fibrosis Score) 2. NASH - steatohepatitis based on FibroScan fibrosis Score at screening (≥7.5 kPa and \<14 kPa (Stage F2-F3) 3. Confirmed medical history of metabolic syndrome 4. Homeostatic Model Assessment of Insulin Resistance (HOMA IR) Score ≥2 5. Confirmed medical history of type 2 diabetes mellitus (T2DM) diagnosis or HbA1c ≥7.0 and \<11 (based on screening values) 6. High total cholesterol ≥240 mg/dL (based on screening values) 7. Hypertension (participants with Stage 1 hypertension (systolic blood pressure \[SBP\] ≥130 mmHg \<180 mmHg, diastolic blood pressure \[DBP\] ≥80 mmHg \<110 mmHg) (based on screening values) * If on medication to manage endocrine/metabolic conditions, must be on stable doses of medication ≥3 months prior to screening: 1. Participants with T2DM may be treated with either diet and exercise alone, metformin, sulphonylurea, thiazolidinediones, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and bromocriptine quick-release (QR) as single agents or combination therapy. 2. As lipid-lowering medication participants may be treated with statins and fibrates, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, ezetimibe, or supplements like omega-3-fatty acids. 3. As antihypertensive medication participants may be treated with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II-inhibitors, diuretics, or calcium channel blockers. * Normal GI function, or abnormalities which the clinical investigator does not consider a disqualification for participation in the study Exclusion Criteria: * Incomplete Coronavirus Disease of 2019 (COVID-19) vaccination * Treatment with weight loss medications in the past 3 months * Proven history of bulimia or anorexia nervosa * Treatment with injectable antidiabetic medications in the last 3 months (e.g. Glucagon-like peptide-1 \[GLP-1\] receptor agonists, insulin) * Treatment with dipeptidyl peptidase-4 inhibitors in the last 3 months * NASH with cirrhosis (fibrosis Score=F4 (≥14 kPa) as determined by screening FibroScan * Confirmed medical history of liver cirrhosis, cholestatic disease, alcohol-related liver disease * Type 1 diabetes mellitus, HbA1c ≥11, fasting plasma glucose levels ≥270 mg/dL * Proliferative retinopathy or maculopathy * Abnormal liver function tests: 1. Transaminases: * Alanine transaminase (ALT)/aspartate aminotransferase (AST) ≥5 x upper limit of normal (ULN) for participants with NAFLD or NASH (as determined by screening FibroScan) * ALT/AST ≥2.5 x ULN for participants without NAFLD or NASH (as determined by screening FibroScan) 2. Alkaline phosphatase (ALK) ≥2.5 x ULN 3. Total bilirubin ≥2 x ULN * Stage 4 hypertension (SBP ≥180, DBP ≥110) * History or presence of any uncontrolled cardiovascular, pulmonary, hepatobiliary, renal, hematologic, gastrointestinal, endocrinologic, immunologic, dermatologic, neurological, psychiatric, metabolic, musculoskeletal, or malignant disease (except conditions accepted for inclusion) which the clinical investigator does not consider a disqualification for participation in the study

Locations (9)

LTD "Israeli-Georgian Medical Research Clinic Healthycore"

Tbilisi, Georgia

LTD "Acad. G. Chapidze Emergency Cardiology Center"

Tbilisi, Georgia

LTD "Diacor"

Tbilisi, Georgia

LTD "National Institute of Endocrinology"

Tbilisi, Georgia

Outcomes

Primary Outcomes

Changes from Baseline in Percent Weight Change Compared with Placebo

Bodyweight measurements will be done using standard personal balance referring to kilogram-Scale. Weighing will be done without shoes and with just underwear on. It is important that weighing is always done in the same way, preferably in the morning, before eating or drinking.

Time frame: At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1

Secondary Outcomes

Percentage of Participants with ≥2.5% Baseline Body Weight Loss at 6 Months Compared with Placebo (Weight Loss Responders)

Body weight measurements will be done using standard personal balance referring to kilogram-Scale. Weighing will be done without shoes and with just underwear on. It is important that weighing is always done in the same way, preferably in the morning, before eating or drinking.

Time frame: At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1

Percentage of Participants with ≥5% Baseline Body Weight Loss at 6 Months Compared with Placebo (Weight Loss Responders)

Body weight measurements will be done using standard personal balance referring to kilogram-Scale. Weighing will be done without shoes and with just underwear on. It is important that weighing is always done in the same way, preferably in the morning, before eating or drinking.

Time frame: At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1

The Difference in Mean Absolute Weight Loss Compared with Placebo at 6 Months

Body weight measurements will be done using standard personal balance referring to kilogram-Scale. Weighing will be done without shoes and with just underwear on. It is important that weighing is always done in the same way, preferably in the morning, before eating or drinking.

Time frame: At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1

Data from ClinicalTrials.gov

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